Timolol
Anton C. de Groot in Monographs in Contact Allergy, 2021
Timolol is a propanolamine derivative and a non-selective β-adrenergic antagonist with antihypertensive property. It competitively binds to β1-adrenergic receptors in the heart and vascular smooth muscle and β2-receptors in the bronchial and vascular smooth muscle, resulting in a decrease in β-adrenergic stimulation. This leads to a decrease in resting and exercise heart rate and cardiac output, and a decrease in both systolic and diastolic blood pressure. β2- blockade results in an increase in peripheral vascular resistance. The ultimate results include vasodilation and negative chronotropic and inotropic cardiac effects. In addition, timolol reduces intra-ocular pressure, possibly by decreasing aqueous humor production from reduction of blood flow to the ciliary processes and reduced cAMP synthesis. The oral form of timolol is used to treat high blood pressure and prevent heart attacks, and occasionally to prevent migraine headaches. Ophthalmic timolol is indicated for the treatment of open-angle and occasionally secondary glaucoma and is the most widely used anti-glaucoma drug (1).
Principles and Methods of Ocular Pharmacokinetic Evaluation
David W. Hobson in Dermal and Ocular Toxicology, 2020
While the distribution of agents after true systemic absorption is addressed below, it is worthy of note that many topically applied drugs are absorbed into the systemic circulation via the nasal mucosa.75,79–86 The loss of compounds into the nasal canaliculi from the ocular surface represents a significant systemic absorption pathway. This route avoids the first-pass effect normally observed after oral presentation of a compound, and the pharmacological sequelae resemble those seen after an intravenous administration. It is important to minimize absorption though this route. Indeed, recommendations for overcoming this pharmacokinetic phenomenon have been given87–89 in clinical situations, since the systemic effects of drugs such as timolol can be quite pronounced.81,90 Occlusion of the nasal punctum for 3 to 5 min is an effective means of both increasing drug uptake by the cornea and reducing systemic side effects. Punctal occlusion obstructs the canaliculi, thereby allowing the possibility of greater ocular uptake of drug by modifying the drainage of fluid from the ocular surface.
Adrenergic Antagonists
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
It is an adrenergic non-selective potent β antagonist. It shows no membrane stabilizing and ISA. It is employed in the treatment of congestive heart failure, hypertension, myocardial infarction, and in managing migraine (Brunton et al., 2011; Florey, 2008; Mayama et al., 2013). In ophthalmology, its use is in treating open angle glaucoma and in intraocular hypertension. It blocks β receptors present in the ciliary epithelium and reduces aqueous humor generation (Chiou et al., 1993; Florey, 2008; Mayama et al., 2013; Van et al., 1990). It shows good absorption from the GIT. The drug attains a peak concentration in the plasma in about 1–2.4 h. The bioavailability is 61–75% due to first-pass metabolism. While used as ophthalmic drops, absorption is fast and the intraocular pressure is lowered within about 3 h. Metabolism happens in liver with the help of CYP2D6 enzyme. After an oral dose first-pass metabolism happens to the drug and its half-life is about 4 h. It can also be useful for patients suffering from coronary cardiac disease (Florey, 2008; Brunton et al., 2011). After an oral dose of timolol the absorption is fast and complete. The drug reaches maximum plasma concentration within 1–2.4 h. The bioavailability is 61–75% due to first-pass metabolism. When used as ophthalmic drops, absorption is rapid and the intraocular pressure is decreased within 3 h. The half-life is approximately 2.5 h. The drug is majorly excreted in the urine (Florey, 2008).
Systemic side effects of glaucoma medications
Published in Clinical and Experimental Optometry, 2022
Amirmohsen Arbabi, Xuan Bao, Wesam Shamseldin Shalaby, Reza Razeghinejad
Timolol, a non-selective beta blocker, is the most commonly prescribed topical beta blocker worldwide. The majority of the reports on beta blockers side effects are on timolol. Arrhythmia, heart failure, syncope, sudden death, bronchospasm, dyspnoea, cerebrovascular accident, recurrent dizziness, worsening of myasthenia gravis, and amaurosis fugax are among the systemic side effects of timolol.61–64 CYP2D6 inhibitors, such as paroxetine, increase the plasma concentration of topical timolol, thereby increasing the risk of adverse cardiovascular effects (orthostatic hypotension, bradycardia, and arrhythmias), especially in elderly patients.65 Third-degree atrioventricular block and sick sinus syndrome were reported with timolol eye drops.66,67 Given the mechanism of action, the side effects of timolol are applicable to other non-selective beta blockers as well.
Fractional 2940-nm Er:YAG laser-assisted drug delivery of timolol maleate for the treatment of deep infantile hemangioma
Published in Journal of Dermatological Treatment, 2021
Li Sun, Chenxia Wang, Yuting Cao, Xinxiang Lv, Limin Tian, Dandan Liu, Lizhong Li, Wenchao Zhao
Infantile hemangiomas (IH) are the most common benign vascular tumors with a reported incidence rate of 4–10% (1,2), and usually appears after several days to several weeks after birth. The initial manifestations of IH include congestive, telangiectatic patches (3). Consecutive photographs of children showed the fastest growth of IH between 5.5 weeks and 7.5 weeks after birth (4), reaching 80% of the final volume by 3 months (5). After that, there is a slow proliferating period from 6 to 9 months, which then gradually fades away after several years (6). IHs are classified into superficial, deep and mixed according to the depth of the tumor (7). Oral propranolol is the first-line treatment for deep IH (3), but is associated with adverse reactions such as hypoglycemia, low blood pressure, slow heart rate, bronchial spasm, wheezing, temporary dyspnea, drowsiness, etc in children (8). In recent years, topical beta blockers were used for treating superficial and deep hemangiomas. Timolol is a nonselective hydrophilic beta blocker (8), and topical treatment of it effectively reduces systemic adverse reactions. Because of the barrier effect of the skin and the hydrophilicity of timolol, the percutaneous penetration of the drug is affected. Hence, fractional 2940-nm Er:YAG laser was used for transdermal delivery of 0.5% timolol maleate eye drops to treat deep IHs in children and evaluate its effectiveness and safety.
Adrenergic agonists and antagonists as antiglaucoma agents: a literature and patent review (2013–2019)
Published in Expert Opinion on Therapeutic Patents, 2019
Alessio Nocentini, Claudiu T. Supuran
The addition of twice-daily timolol 0.5% to nine patients being treated with latanoprost 0.005% resulted in an additional reduction in IOP of 14% [38]. Once daily application of latanoprost combined with twice daily timolol proved to be more effective than twice daily application latanoprost [39]. Stewart et al. found a reduction in IOP ranging from 14 to 21% in the PGA-treated baselines of 30 patients with open-angle glaucoma or ocular hypertension following 6 weeks of therapy with topical timolol 0.5% [40]. Clearly, from a dose regimen point of view, the two drugs are difficult to combine into one and get a full additive effect. The prostaglandin should be optimally instilled once daily to get the peak effect during the morning hours when IOP is physiologically at its highest [37]. Timolol is instead usually administered twice daily. Despite these challenges, additional IOP reduction is achieved with the combination products in comparison with the monotherapies [10,37].
Related Knowledge Centers
- Angina
- Beta Blocker
- Bradycardia
- Glaucoma
- Intraocular Pressure
- Myocardial Infarction
- Ocular Hypertension
- Hypertension
- Eye Drop
- Migraine